Weight problems in Focus: ADA Reveals R&D Priorities for Blockbusters-in-Ready

Regardless of not being within the occasion title, weight reduction and weight problems took heart stage on the just lately concluded 2025 Scientific Classes of the American Diabetes Affiliation.

That a lot isn’t shocking. Weight problems is the most well liked factor entering into biopharma, a lot in order that analysts now count on the market to hit an eye-watering $150 billion yearly by the early 2030s.

Subsequent-generation approaches are anticipated to play a key position, and so they have been on full show at ADA, with lots of the largest shows specializing in methods to enhance on current remedies by means of safer regimens, extra handy dosing and even new pathways to elicit higher weight reduction.

“What’s lacking from the weight problems area is a stronger deal with affected person expertise—particularly ease of use, accessibility, and preserving muscle mass,” John Gagliano, senior director at BioPharmCatalyst, informed BioSpace in an e mail.

Regardless of current medicine’ efficacy in chopping physique weight, many sufferers are nonetheless discouraged from taking them, Gagliano mentioned, due to “frequent injections, issues about weak point, or undesirable muscle loss.” Corporations on this area, he added, would do nicely to “prioritize lifestyle-friendly remedies.”

Samuel Redfern, affiliate analyst of prescription drugs at BMI, a FitchSolutions Firm, agreed, telling BioSpace in an e mail that whereas sufferers discontinue weight reduction remedy for quite a lot of causes, “gastrointestinal side-effects and muscle loss are key drawbacks of current GLP-1 therapies.” Exploring new mechanistic pathways, similar to concentrating on amylin or preserving muscle, he continued, may end in new remedies which can be as efficient however don’t have these drawbacks, permitting them to “drive long-term progress” on this area.

Biopharma is on the case, and several other firms showcased their most up-to-date developments at ADA final month.

Weight reduction leaders Novo Nordisk and Eli Lilly offered updates on CagriSema and orforglipron, respectively, each of which have been positioned as successors to those firms’ present blockbuster franchises. The convention additionally noticed shows from different weight problems gamers, together with Amgen on its GLP-1/GIP analog MariTide and Innovent on its GLP-1/glucagon twin agonist mazdutide.

Right here, BioSpace friends additional into the way forward for the weight problems area.

Lilly’s Bimagrumab Preserves Muscle in Mid-Stage Trial

El Lilly’s oral GLP-1 agonist orforglipron stole the highlight at ADA 2025 for good cause: The drug just lately cleared a Part III diabetes trial, the place it confirmed “injectable-like efficacy,” in keeping with analysts at BMO Capital Markets. One other readout, this time in weight problems, is slated for the third quarter.

However simply as compelling is the pharma’s bimagrumab, a mid-stage antibody that targets activin/myostatin kind II receptors, that are concerned in signaling cascades that counteract muscle progress. Bimagrumab’s mechanism not solely prevents muscle loss however may also promote a rise in muscle.

Lilly introduced information from the Part IIb BELIEVE trial at ADA, demonstrating that bimagrumab, when used with rival Novo Nordisk’s blockbuster GLP-1 drug Wegovy (semaglutide), can decrease physique weight by 22.1% at 72 weeks. Notably, 92.8% of this weight reduction is attributable to fats—solely round 7% was because of the losing of lean mass.

Contributors who got bimagrumab alone misplaced 10.8% of their physique weight at 72 weeks, 100% of which was resulting from fats loss.

These information may place bimagrumab nicely for the longer term weight-loss remedy area envisioned by Redfern, the place “cornerstone” remedies like Lilly’s Zepbound (tirzepatide) and Wegovy can be “utilized in mixture with new mechanisms of motion that mitigate their much less fascinating results.”

Analysts at BMO Capital Markets are equally optimistic about bimagrumab. Writing to traders on June 23, they referred to as the candidate’s efficiency in BELIEVE “sturdy” and “spectacular,” with its weight reduction numbers offering a “clear constructive for constructing a regulatory approval case for physique composition belongings.”

Not all are satisfied, nevertheless. Leerink Companions in a June 24 word expressed concern about “a number of tolerability/security flags within the information,” including that top charges of muscle spasms, diarrhea and pimples alongside elevated ranges of low-density lipoprotein ldl cholesterol and liver enzymes “cloud bimagrumab’s general profile and make business prospects unclear.”

“We proceed to mannequin zero gross sales for bimagrumab,” the analysts wrote.

Novo Fights For Amylin Lead With Amycretin—However Knowledge Stay Combined

Amylin, a pancreatic peptide that lowers blood sugar ranges and suppresses urge for food, has just lately grow to be a contested frontier within the weight reduction area. With the late-stage CagriSema, a mixture routine consisting of semaglutide and the long-acting amylin mimetic cagrilintide, Novo is arguably on the head of the pack.

However CagriSema has run into its fair proportion of troubles: A December 2024 Part III readout fell wanting expectations, sparking a selloff that wiped some $72 billion off the pharma’s market cap.

In a bid to keep up its amylin lead—and regain some investor confidence—Novo is now seeking to transfer its next-generation remedy amycretin shortly by means of the clinic. The drug, which additionally targets each GLP-1 and amylin, elicited weight lack of as much as 22% after 20 weeks when given as a 20-mg subcutaneous dose in a Part Ib/IIa trial, Novo reported in January.

Reacting to those outcomes, BMO analysts on the time mentioned that amycretin “may begin to shift the narrative round Novo shares with a next-gen remedy within the firm’s pipeline that may very well be aggressive with the likes of Lilly’s tirzepatide and retatrutide.”

Novo launched follow-on information at ADA, noting that after 36 weeks of remedy with doses as excessive as 60 mg, sufferers noticed a 24.3% discount in weight. This dipped barely to 23.2% after correcting for placebo.

Nonetheless, analysts stay tempered of their optimism over amycretin. Reacting to Novo’s ADA presentation, William Blair informed traders in a June 23 word that whereas amycretin’s 36-week weight reduction was spectacular, “the excessive frequency of opposed occasions may gas uncertainty over the asset’s differentiation in opposition to authorized or late-stage investigational compounds.”

However, Novo seems dedicated to its next-generation amylin asset, asserting at ADA that it’s going to take each subcutaneous and oral formulations of amycretin “straight to section 3 improvement for weight administration.” The pharma will launch its late-stage program for amycretin within the first quarter of 2026.

Zealand Targets Two GLP Receptors to Deal with Underlying Weight problems Irritation

Zealand Pharma is seeking to innovate on the present GLP-1 strategy to weight problems by including a molecular cousin into the combo: GLP-2.

At ADA, the Danish biotech touted Part Ib information for its investigational subcutaneous injection dapiglutide, which prompts each the GLP-1 and GLP-2 receptors. This distinctive mechanism of motion—one Zealand claims is probably first-in-class—permits dapiglutide to not solely elicit the standard metabolic advantages of GLP-1 agonists, but additionally deal with low-grade irritation linked to the GLP-2 pathway.

In a June 19 word to traders, analysts at William Blair famous that the involvement of GLP-2 may very well be “significantly helpful” for dapiglutide, giving it the potential to deal with circumstances adjoining to weight problems, similar to heart problems, leaky intestine, liver illness and neurological irritation.

“Zealand is positioning dapiglutide as a remedy that might each induce weight reduction and probably cut back the chance of obesity-related well being outcomes, which we argue may have a extra significant public well being implication,” William Blair wrote.

In its ADA readout, Zealand touted weight lack of 11.6% over 28 weeks of remark, a determine William Blair argued may be an underrepresentation of dapiglutide’s true efficacy.

William Blair, in its word, flagged the “atypical” traits of Zealand’s research pattern. Greater than 90% of the members have been male, for example, and had a “comparatively low baseline physique weight” of roughly 92 kg. When examined in a “extra consultant inhabitants”—as in a pattern with a extra balanced intercourse break up or in people who find themselves obese or overweight at baseline—dapiglutide may present even increased weight reduction numbers, the analysts mentioned.

In accordance with its Q1 report, Zealand expects to provoke a Part II trial of dapiglutide this 12 months.

Scholar Rock’s SMA Drug Exhibits Muscle-Preserving Potential in Weight problems

Like Lilly, Scholar Rock is working to enhance the standard of weight reduction by preserving lean mass. In contrast to Lilly, the Massachusetts-based biotech is specializing in only one muscle molecule: myostatin.

A part of the TGFβ superfamily of progress elements, myostatin is a signaling protein that suppresses the event of skeletal muscle tissues. Apitegromab targets each energetic and latent types of myostatin, a mechanism of motion that might result in “more healthy weight reduction” in sufferers on weight problems drugs, Akshay Vaishnaw, president of R&D at Scholar Rock, mentioned in a June 18 launch.

Olivia Tidwell, content material coordinator at BioPharmCatalyst, agreed. “Whereas most weight problems remedies deal with complete weight reduction, apitegromab uniquely addresses the preservation of lean muscle mass—a rising concern with GLP-1 therapies like tirzepatide, which might trigger important muscle loss,” she informed BioSpace. “Apitegromab provides a differentiated strategy with potential worth in a broad cardiometabolic inhabitants.”

Knowledge introduced at ADA, from the Part II EMBRAZE trial, confirmed that over 24 weeks of remedy, sufferers handled with each apitegromab and Lilly’s trizepatide misplaced 3.4 lbs of lean mass, versus 7.6 lbs in these given tirzepatide alone. The distinction of 4.2 lbs represented a practically 55% muscle preservation benefit within the apitegromab arm, Scholar Rock introduced on the time.

EMBRAZE discovered apitegromab to be secure and well-tolerated, with opposed occasions arising comparably between remedy arms. There have been no critical opposed occasions or research dropouts associated to apitegromab, and no affected person deaths.

The candidate additionally had a clear security profile, Jefferies wrote, “which is likely one of the key benefits of extra selectively concentrating on latent myostatin vs broadly concentrating on myostatin + activin A.”

Scholar Rock’s lead indication for apitegromab is spinal muscular atrophy (SMA), a genetic neuromuscular dysfunction. Apitegromab is at the moment present process regulatory overview on this indication, with a verdict anticipated on Sept. 22. An SMA approval could be a “main de-risking occasion” for apitegromab, Jefferies famous.

Terns Targets Thyroid Hormone Receptors

Closing out this checklist is an asset that wasn’t featured at ADA however nonetheless provides a novel strategy to weight problems: Terns Prescription drugs’ THR-β agonist TERN-501.

TERN-501 works by activating the beta subtype of the thyroid hormone receptor (THR), which performs a key position in regulating a number of metabolic processes. Although not as extensively studied as GLP-1, the THR pathway additionally presents a promising goal for weight problems remedy, with a number of research displaying that agonists to this receptor might help management lipid and levels of cholesterol whereas additionally boosting metabolic fee.

Nonetheless, THR modulators have additionally been linked to cardiovascular problems, which restrict their use in managing physique weight. That is the place Terns is seeking to distinguish itself. In accordance with the biotech’s web site, TERN-501 is designed to be particularly selective for THR-β, with enhanced distribution within the liver—a declare backed by preclinical information demonstrating a 23-fold higher selectivity for this particular subtype of the receptor in contrast with the THR-α subtype. This selectivity “[minimizes] the chance of cardiotoxicity and different off-target results,” in keeping with Terns.

In June 2024, the biotech launched preclinical information demonstrating that when used with Novo’s semaglutide, TERN-501 can elicit considerably higher weight reduction in mouse fashions as in contrast with semaglutide alone. Weight discount gave the impression to be largely attributable to fats loss: sufferers handled with TERN-501 plus semaglutide noticed a considerably higher lower in fats mass versus comparators on semaglutide alone.